Certain techniques, such as in analytical chemistry, require that components of a sample be ionized prior to analysis. Mass spectrometry (MS) is an example of such analytical techniques. Generally, MS describes a variety of instrumental methods of qualitative and quantitative analysis that enable sample components to be resolved according to their mass-to-charge ratios. For this purpose, an MS system converts the components of a sample into ions, sorts or separates the ions based on their mass-to-charge ratios, and processes the resulting ion output (e.g., ion current, flux, beam, etc.) as needed to produce a mass spectrum. Typically, a mass spectrum is a series of peaks indicative of the relative abundances of charged components as a function of mass-to-charge ratio (typically expressed as m/z or m/e, or simply “mass” given that the charge z or e often has a value of 1).
Insofar as the present disclosure is concerned, MS systems are generally known and need not be described in detail. Briefly, a typical MS system generally includes a sample inlet system, an ion source or ionization system, a mass analyzer (also termed a mass sorter or mass separator) or multiple mass analyzers, an ion detector, a signal processor, and readout/display means. Additionally, the MS system may include an electronic controller such as a computer or other electronic processor-based device for controlling the functions of one or more components of the MS system, storing information produced by the MS system, providing libraries of molecular data useful for analysis, and the like. The electronic controller may include a main computer that includes a terminal, console or the like for enabling interface with an operator of the MS system, as well as one or more modules or units that have dedicated functions such as data acquisition and manipulation. The MS system also may include a vacuum system to enclose the mass analyzer(s) in a controlled, evacuated environment. In addition to the mass analyzer(s), depending on design, all or part of the sample inlet system, ion source, and ion detector may also be enclosed in the evacuated environment. Certain types of ion sources or interfaces operate at or near atmospheric pressure and thus are distinct from the vacuum or low-pressure regions of the mass analyzer.
In operation, the sample inlet system introduces a small amount of sample material into the ion source. Depending on design, all or part of the sample inlet system may be integrated with the ion source. In hyphenated techniques, the sample inlet system may be the output of an analytical separation instrument such as a gas chromatographic (GC) instrument, a liquid chromatographic (LC) instrument, a capillary electrophoresis (CE) instrument, a capillary electrochromatography (CEC) instrument, or the like. The ion source converts components of the sample material into a stream of positive and negative ions. One ion polarity is then accelerated into the mass analyzer. The mass analyzer separates the ions according to their respective mass-to-charge ratios. The mass-resolved ions outputted from the mass analyzer are collected at the ion detector. The ion detector is a type of transducer that converts ion current to electrical current, thereby encoding the information represented by the ion output as electrical signals to enable data processing by analog and/or digital techniques.
Several different approaches may be taken for effecting ionization. Hence, various designs for ion sources have been developed. The present disclosure relates primarily to a class of ionizing techniques known as atmospheric pressure ionization (API) in which ionization of sample material occurs at or near atmospheric pressure, after which time the resulting ions are transferred to the mass spectrometer. For convenience, the term “mass spectrometer” is used herein in a general, non-limiting sense to refer to a mass analyzing/sorting device and any associated components typically operating within an evacuated space that receives an input of sample material from the API interface. Examples of API techniques include electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI or APcI), and atmospheric pressure photoionization (APPI). API techniques are particularly useful when it is desired to couple mass spectrometry with an analytical separation technique such as liquid chromatography (LC), including high-performance liquid chromatography (HPLC). For instance, the output or effluent from an LC column can serve as the sample source or input into an API interface. Typically, the effluent consists of a liquid-phase matrix of analytes (for example, molecules of interest) and mobile-phase material (for example, solvents and additives).
ESI is a type of desorption ionization technique in which energy is applied to a sample liquid so as to cause direct formation of gaseous ions. A typical ESI source includes a chamber held at atmospheric pressure (or near atmospheric pressure). This chamber is separated from one or more vacuum or low-pressure regions of the mass spectrometer in which the mass analyzing and ion detection components reside. Sample liquid is introduced into the chamber through a capillary tube or electrospray needle. A voltage potential is applied between the electrospray needle and a counter-electrode that may be a surface or other structure within the chamber, thereby establishing an electric field within the chamber. The electric field induces charge accumulation at the surface of the liquid at or near the tip of the electrospray needle, and the liquid is discharged from the needle in the form of highly charged droplets (electrospray). The breaking of the stream of liquid into a mass of fine droplets, or aerosol, may be assisted by a nebulizing technique that may involve pneumatic, ultrasonic, or thermal means. For example, pneumatic nebulization may be implemented by providing a tube coaxial to the electrospray needle and discharging an inert gas such as nitrogen coaxially with the sample liquid. An electric field directs the charged droplets from the tip of the electrospray needle toward a sampling orifice that leads from the chamber to the mass spectrometer. The droplets undergo a process of desolvation or ion evaporation as they travel through the chamber and/or through a conduit associated with the sampling orifice. As solvent contained in the droplets evaporates, the droplets become smaller. In addition, the droplets may rupture and divide into even smaller droplets as a result of repelling coulombic forces approaching the cohesion forces of the droplets. Eventually, charged analyte molecules (analyte ions) desorb from the surfaces of the droplets. Ideally, only the analyte ions enter the mass spectrometer, and not the other components of the electrospray such as neutral solvated droplets. A stream of an inert drying gas such as nitrogen may be introduced into the chamber to assist in the evaporation of solvent and/or sweep the solvent away from the sampling orifice. The drying gas may be heated prior to introduction into the chamber. Conventionally, the drying gas is introduced through an annular opening formed by a tube that is coaxial with the sampling orifice. That is, the drying gas is introduced coaxially and in counterflow relation to the electrospray as the electrospray approaches the sampling orifice. Alternatively, the drying gas is introduced as a curtain in front of the sampling orifice.
Unlike ESI, APCI is a type of gas-phase ionization technique that requires nebulization and vaporization of the sample liquid prior to ionization. It will be noted, however, that some commercially available API sources are readily interchangeable between ESI and APCI modes of operation, and in analytical practice these two modes can be complementary and thus highly useful. Like the ESI source, a typical APCI source includes an atmospheric-pressure chamber separated from the mass spectrometer. Sample liquid is introduced into a pneumatic nebulizer in which an inert nebulizing gas such as nitrogen, flowing concentrically with the stream of sample liquid, breaks the liquid stream into droplets. The sample droplets then flow through a heated vaporization chamber or tube to vaporize the mobile phase and other components of the droplet matrix. The resulting gas-phase droplet dispersion is then discharged into the chamber. An electrode such as a corona discharge needle extends into the chamber and emits electrons. As a result, a corona discharge is generated in the chamber. The corona discharge ionizes the mobile-phase molecules to form an energetic, chemical-reagent gas plasma. In the corona discharge, ion-molecule reactions occur between the charge-neutral sample and the reagent ions formed in the primary discharge. The ion-molecule reactions in turn cause the sample components to become charged, and the resulting analyte ions are directed toward a sampling orifice that leads from the chamber to the mass spectrometer. A voltage potential may be impressed between, for example, the corona discharge needle and a counter-electrode such as a plate surrounding the sampling orifice to guide the analyte ions toward the sampling orifice. Similar to the above-described ESI source, a flow of drying gas may be introduced coaxially and in counterflow relation to the analyte ion flux as the flux approaches the sampling orifice, or introduced as a curtain in front of the sampling orifice, to prevent entry of neutral droplets into the mass spectrometer.
In the APPI technique, similar to APCI, sample liquid flows through a nebulizer, the resulting droplets flow through a vaporizer, and the resulting vaporized droplet matrix is introduced into an atmospheric-pressure chamber. The droplets are then irradiated by photons emitted from a photon source such as an ultraviolet (UV) lamp or other suitable device. The photon source may be positioned near the exit orifice of the vaporizer from which the droplets are introduced into the chamber, or integrated with the vaporizer, or otherwise positioned to ensure that the path of the photons will encounter the path of the droplets. The droplet matrix is ionized through collisions between the photons and the components of the matrix. As in other techniques, an electric field may be established in the chamber to guide the ions toward the sampling orifice. In addition, a counterflow of drying gas coaxial with the sampling orifice that leads to the mass spectrometer, or alternatively a curtain of drying gas, may be utilized to prevent entry of unwanted droplets into the mass spectrometer.
A recurring problem in API techniques such as those described above is the entry of unwanted droplets and other non-analytical material into the sampling orifice. Such unwanted components may degrade the performance of the mass spectrometer and/or the quality of the mass spectral data produced thereby, through contamination, reduction in sensitivity, reduction in robustness, peak tailing, et cetera. These problems can be exacerbated as the flow rate of sample material introduced into the ion source is increased. As previously noted, the ion source has conventionally been provided with a counterflow or a curtain of a heated, dry inert gas such as nitrogen to protect the sampling orifice by blowing away the unwanted components. These previous approaches, however, have failed to sufficiently appreciate that the entry of unwanted components into the sampling orifice may be enhanced by increasing or promoting the transfer of heat energy from the drying gas to the droplets in the chamber to thereby increase evaporation. While the flow rate and temperature of drying gas could be varied for this purpose, and often is varied to accommodate different mobile-phase compositions, the ranges over which these parameters can be varied is limited in practice. The flow rate of the drying gas cannot be so great as to prevent the analyte ions from entering the sampling orifice. Moreover, the temperature of the drying gas cannot be so great as to thermally degrade the analyte ions, or to otherwise adversely affect the analyte ions or impair the performance of the mass spectrometer.
Accordingly, there continues to be a need for improving evaporation of droplets in an ion source, and for protecting the mass spectrometer or other analytical instrument to which the ion source is coupled from the droplets, in order to improve the performance of the analytical instrument and the quality of the data produced thereby, such as by increasing sensitivity, reducing noise, and reducing contamination. The present disclosure recognizes that a flow of drying gas into an appropriately designed ion source can establish a heated zone or area in which heat energy is transferred from the drying gas to the sample material in the ion source. In conventionally designed ion sources, the flow of drying gas is focused only at the region immediately in front of the sampling orifice, and primarily as a single, concentrated flow path. Consequently, the heated zone in which the drying gas can encounter sample material is too small and, consequently, limits the process of evaporation.